References : 1. ATAC Completed Treatment Analysis: Anastrozole demonstrates superior efficacy and tolerability compared with tamoxifen. Howell A on behalf of the ATAC Trialists Group San Antonio 2004. 2. ATAC Trialists Group. Results of the ATAC (Arimidex, Tamoxifen Alone or in combination) Trial after Completion of 5 years adjuvant treatment for breast cancer. Lancet 2005;365(9453):60-62. 3. American Society of Clinical Oncology Technology: Status Report 2004, JCinOncol : 23(3), 2005 ; 619-629 4. National COmprehensive Cancer Network, Clinical Practice Guideline in Oncology, Breast Cancer, version 1. 2005 anastrozole
CONTENTS No. 4 2008 APRIL The convenient medication The efficacy duration The improved efficacy The cost effectiveness Upfront 04 05 06 12 14 19 24 30 38 Education - Clinical and basic oncology forum Basic molecular oncology Cancer stem cells Supportive care in cancer patients Cancer targeted therapy Genomics: from bench to clinics Education - Recent interesting paper in oncology 48 52 56 Breast cancer Colorectal cancer Stomach cancer News & Activity 60 63 64 66 68 www.aloxi.com
NEWS & EDUCATION 2008 APRIL No. 4 UPFRONT
UPFRONT Letter 4 APRIL 2008 KSCO NEWS & EDUCATION 5
INTERVIEW - 6 APRIL 2008
1 2 3 4 8 APRIL 2008 KSCO NEWS & EDUCATION 9
10 APRIL 2008 KSCO NEWS & EDUCATION 11
UPFRONT Information EDUCATION CLINICAL AND BASIC ONCOLOGY FORUM 12 APRIL 2008
EDUCATION Basic molecular oncology (oncogene) (tumor suppressor) 14 APRIL 2008 KSCO NEWS & EDUCATION 15
EDUCATION Basic molecular oncology 16 APRIL 2008 KSCO NEWS & EDUCATION 17
EDUCATION Basic molecular oncology (self renewal pathway) 18 APRIL 2008 KSCO NEWS & EDUCATION 19
EDUCATION Cancer Stem Cells a b c d Niche cell Stem cell Differentiated progeny Transforming mutation ENT Niche ECM Fig.1. Potential models of transformation involving stem cells. (a)the organization of a normal epithelial tissue including a stem cell and its niche. (b)tumor initiated by a single mutation that disrupts the regulation of asymmetric division in stem cells. These mutated cancer stem cells differentiate into committed daughter cells that accrue other mutations, leading to a fully transformed cell. (c)tumor initiated by a cancer stem cell that harbors a combination of mutations that suffice to program the malignant state. (d)tumor initiated by mutations in committed daughter cells that induce dedifferentiation through an epithelial-mesenchymal transition. Such cells mimic features of normal stem cells but are not true stem cells. Signaling cells HH antagonists Responding cells Agents blocking transportation Compounds blocking Gli activity,such as forskolin Hip Ptch Smo Fu Gli Gli SuFu Shh,Ihh,Dhh Cyclopamine Transcriptional repression or activation Target genes cytoplasm membrane nucleus Fig.2. A schematic diagram for the hedgehog(hh) signaling pathway. Ligands, such as Sonic Hedgehog(Shh), Indian Hedgehog(Ihh), and Desert Hedgehog(Dhh), are secreted by signaling cells and bind the transmembrane receptor patched(ptch) in HH responding cells. In the absence of ligands, Ptch binds to Smoothened(Smo) and blocks Smo s function, whereas this inhibition is relieved in the presence of ligands, and Smo initiates a signaling cascade that results in the release of transcription factors Glis from cytoplasmic proteins fused(fu) and suppressor of fused(sufu). In the inactive situation, SuFu prevents Glis from translocationg to the nucleus: in the active situation, Fu inhibits SuFu and Glis are released. Gli proteins translocate into the nucleus and control target gene transcription. The red lines and the agents in red show the inhibitors of this pathway with potential therapeutic value. 20 APRIL 2008 KSCO NEWS & EDUCATION 21
EDUCATION Cancer Stem Cells DSL DSL membrane Fringe Presenilin cytoplasm nucleus Fig.3. A schematic diagram for the Notch signaling pathway. Upon binding of the DSL ligand, Notch signaling is modulated by fringe, and Notch receptors are activated by serial cleavage events involving memebers of the ADAM(for a disintegrin and metalloproteinase )protease family, as well as an intramembrane cleavage regulated by gamma-secretase(presenilin). This intrmembrane cleavage is followed by translocation of the intracellular domain on Notch to the nucleus, where it acts on downstream targets. CBF, c promoter binding factor; HDAC, histone deacetylase; HAT, histone acetyltransferase. (a) Fz Dsh WNT LRP 5/6 Axin GSK-3 APC -catenin -catenin TCF Wnt target genes (b) Fig.4 A schematic diagram for the Wnt signaling pathway.(a)the canonical Wnt/ catenin pathway. (b) The noncanonical Wnt signaling pathway. Fz CamKll PKC WNT Ca ++ Cellular responses Knypek Dsh Daam1 Rho Cdc42 Rac 22 APRIL 2008 KSCO NEWS & EDUCATION 23
EDUCATION Supportive care in cancer patients Fig.1. Neuronal pathways in chemotherapy-induced nausea and vomiting Chemotherapy (chemotherapy-induced nausea and vomiting; CINV) Higher cortical centers Serotonin is released from enterochromaffin cells of GI tract 5-HT3 NK-1 dopamine Chemoreceptor trigger zone Vestibular apparatus dopamine 5-HT NK-1 Vomiting center Vagus nerve afferents H1 Salivatory Respiratory Vasomotor Abdominal muscles Diaphragm Stomach Vomiting Muscarinie 24 APRIL 2008 KSCO NEWS & EDUCATION 25
EDUCATION Supportive care in cancer patients Table 1. Risk factors for CINV Patient specific Chemotherapy specific Female Previous episode Age; 6 yrs<, 50 yrs > Higher dose <100g ethanol intake/day for several yrs Multiple dose Tendency of motion sickness Multiple agents Tendency for anxiety History of hyperemesis with pregnancy Table 2. The risk and management in chemotherapy-induced nausea and vomiting Risk Frequency of N/V Minimal < 10% Bleomycin Busulfan Methotrexate (<50mg/m2) Hydroxyurea(oral) Vincristine Chlorambucil Thalidomide Vincristine No routine prophylaxis If nausea or vomiting develops, consider using antiemetics 5-Fluorouracil Dexamethasone 12mg daily Docetaxel or Prochloperazine 10mg every 4~6 hours Gemcitabine or Metochlopramide 10~40mg every 4~6 hr Low 10% ~ 30% Doxorubicin(liposomal) +/- antihistamine Paclitaxel +/- Lorazepam 0.5~2mg every 4~6 hours Methotrexate (250~1000mg/m2) Busulfan(>4mg/d) Aprepitant 125mg or Aprepitant 80mg if used Doxorubicin Dexamethasone 12mg on Day 1 or Carboplatin and 5-HT3 antagonist Dexamethasone 8mg Epirubicin or 5-HT3 antagonist Cisplatin(<50mg/m2) Moderate 30% ~ 90% Irinotecan If necessary, If necessary, Daunorubicin Lorazepam 0.5~2mg Lorazepam 0.5~2mg Melphalan(>50mg/m2) Every 4~6 hours Every 4~6 hours Oxaliplatin Cyclophosphamide (<1500mg/m2) High > 90% Agents D1 D2-3 Cisplatin(>50mg/m2) Aprepitant 125mg & Aprepitant 80mg Cyclophosphamide Dexamethasone 12mg Dexamethasone 8mg (>1500mg/m2) & 5-HT3 antagonist Mechlorethamine Doxorubicin or epirubicin If necessary, If necessary, with cyclophosphamide Lorazepam 0.5~2mg Lorazepam 0.5~2mg every 4~6 hours every 4~6 hours 26 APRIL 2008 KSCO NEWS & EDUCATION 27
EDUCATION Supportive care in cancer patients 28 APRIL 2008 KSCO NEWS & EDUCATION 29
EDUCATION Cancer targeted therapy 30 APRIL 2008 KSCO NEWS & EDUCATION 31
EDUCATION Cancer targeted therapy 32 APRIL 2008 KSCO NEWS & EDUCATION 33
EDUCATION Cancer targeted therapy 34 APRIL 2008 KSCO NEWS & EDUCATION 35
EDUCATION Cancer targeted therapy 36 APRIL 2008 KSCO NEWS & EDUCATION 37
EDUCATION Genomics: from bench to clinics Transcriptome and Epigenome Study of Cancer Cell 38 APRIL 2008 KSCO NEWS & EDUCATION 39
EDUCATION Genomics: from bench to clinics MD Mglio Rhab Ncer PNET 40 APRIL 2008 KSCO NEWS & EDUCATION 41
EDUCATION Genomics: from bench to clinics ON OFF 42 APRIL 2008 KSCO NEWS & EDUCATION 43
EDUCATION Genomics: from bench to clinics a. Restriction enzyme b. Bisulphite treatment c. mclp d. Chlp Hpoll Bisulphite Sonication Msel digestion lmmunopercipitation Adaptor ligation PCR lmmunopercipitation Hpoll digestion DNA purification and amplification Labeling Hybridization to Tiling Array 44 APRIL 2008 KSCO NEWS & EDUCATION 45
EDUCATION RECENT INTERESTING PAPERS IN ONCOLOGY
EDUCATION Breast cancer 01 02 48 APRIL 2008 KSCO NEWS & EDUCATION 49
EDUCATION Treatise 03 04 Induction chemotherapy (n= 386) Enrollment less than PR to induction chemotherapy ( n=62) ; not randomly assigned Randomly assigned High dose chemotherapy & ASCT ( n=112) standard dose chemotherapy ( n=112) Received ASCT ( n=91) Ineligible ;< PR to induction (n=1) Received high dose chemotherapy ( n=2) Did not receive ASCT ( n=21) Reason; Disease progression ( n=11), Refusal (n= 6) Toxicity (n=2 ), Inadequate stem cell collection ( n=2) Analyzed ( n=112) Analyzed ( n=111) ASCT : Autologous Stem Cell Transplantation 50 APRIL 2008 KSCO NEWS & EDUCATION 51
EDUCATION Colorectal cancer 01 02 52 APRIL 2008 KSCO NEWS & EDUCATION 53
03 04 05 06 54 APRIL 2008 KSCO NEWS & EDUCATION 55
EDUCATION Stomach cancer 01 02 04 03 56 APRIL 2008 KSCO NEWS & EDUCATION 57
NEWS & ACTIVITY
NEWS & ACTIVITY KOREAN SOCIETY NEWS KOREAN SOCIETY NEWS 60 APRIL 2008 KSCO NEWS & EDUCATION 61
NEWS & ACTIVITY KOREAN SOCIETY NEWS FOREIGN SOCIETY NEWS 62 APRIL 2008 KSCO NEWS & EDUCATION 63
NEWS & ACTIVITY KSCO NEWS 64 APRIL 2008 KSCO NEWS & EDUCATION 65
UPFRONT Letter 67 APRIL 2008
68 APRIL 2008 KSCO NEWS & EDUCATION 69